Acute leukoencephalopathy possibly induced by phenytoin intoxication in an adult patient with methylenetetrahydrofolate reductase deficiency

Abstract

SUMMARYA 19-year-old university student with no personal or family history of neurologic disorders developed convulsions and was administered phenytoin. Two months later, he developed lower limb-dominant acute demyelinating polyneuropathy, from which he recovered within 2 months. At age 20, he rapidly developed visual disturbances and paraplegia from phenytoin intoxication. Cranial magnetic resonance imaging (MRI) revealed leukoencephalopathy with no evidence of thrombosis or vasoconstriction. Hyperhomocysteinemia, hypomethioninemia, low serum folate concentration, and an absence of megaloblastic anemia were consistent with the diagnosis of methylenetetrahydrofolate reductase (MTHFR) deficiency. A genomic DNA sequence analysis demonstrated compound heterozygosity for two missense mutations in the MTHFR gene, namely, [458G>T + 459C>T] (Gly149Val) and 358G>A (Ala116Thr), both of which are known pathogenic mutations. An absence of leukoencephalopathic changes on MRI scans performed 9 months previously strongly suggested that phenytoin intoxication caused acute leukoencephalopathy. Therefore, phenytoin may be an aggravating factor of remethylation defects in patients with MTHFR deficiency.

Influence of anti-epileptic drugs on hematological and biochemical parameters in patients with epilepsy

“…6 Published literature suggests that changes in hematological parameters such as Hb over 12 months is inversely associated with a subsequent risk of morbidity and mortality, independent of the effects of baseline anemia and other important predictors. 10 A statistically significant difference was also noticed in ALP levels between monotherapy and polytherapy, where polytherapy had greater influence on ALP levels, a finding similar to the study by Tolou-Ghamari et al 5 ALP is considered to be the marker for hepatocellular activity. However, an increase in the ALP levels may be due to increase in the osteoblastic activity.…”

Rapidly progressive psychotic symptoms triggered by infection in a patient with methylenetetrahydrofolate reductase deficiency: a case report

“…Previously, rapidly deteriorating psychosis was reported in the case of adolesecent- or adult-onset MTHFR deficiency [ 7 – 10 ]. The reason for rapid deterioration in these patients is not known; but the lack of dietary supplements, the use of nitrous oxide during general anesthesia, and long-term use of the antiepileptic drug phenytoin have been reported as risk factors for acute neurological deterioration [ 3 , 11 ]. So, we speculate that the change in nutritional status through reductions in dietary intake and intestinal absorption due to gastroenteritis might have been responsible for the rapid deterioration seen in our patient.…”

Guidelines for diagnosis and management of the cobalamin‐related remethylation disorders cblC, cblD, cblE, cblF, cblG, cblJ and MTHFR deficiency

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